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Trial · Interventional

TerminatedPhase 2Results postedRegistry data

Prospective, Open-Label, Multicenter, International Study of Mifepristone for Symptomatic Treatment of Cushing's Syndrome Caused by Ectopic Adrenal Corticotrophin Hormone (ACTH) Secretion

NCTNCT00422201 (opens ClinicalTrials.gov in a new tab)Other id070008Other id07-CH-0008
Open at ClinicalTrials.govAsk about this trial

This trial does not test a peptide that PepBank tracks.

  • Measures ACTH (corticotropin), does not give it. It appears in the eligibility rules.

Overview

Status
Terminated
Phase
Phase 2
Enrollment
18 participants (actual)
Sponsor
HRA Pharma · Industry
Design
Allocation not applicable · Open label (no masking)
Countries
5 countries

United States, France, Germany, Italy, Netherlands

Start
15 May 2007
Primary completion
4 Apr 2012
Completion
4 Apr 2012
First posted
15 Jan 2007 (estimated)
Last update posted
11 Oct 2019
Conditions
Cushing's Syndrome

Timeline

1 trial · 1 stopped early · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2007200820092010201120122013
  1. Ph 2

    Prospective, Open-Label, Multicenter, International Study of Mifepristone for Symptomatic Treatment of Cushing's Syndrome Caused by Ectopic Adrenal Corticotrophin Hormone (ACTH) Secretion

    NCT00422201

    15 May 2007 to 4 Apr 2012

    Terminated

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

This study will evaluate whether the drug mifepristone can improve the symptoms of Cushing's syndrome in people with ectopic adrenal corticotrophin hormone (ACTH) secretion. Cushing's syndrome occurs when the adrenal glands produce too much cortisol, a hormone that helps to regulate the body's use of salt and food. Excessive cortisol is usually the result of too much ACTH, the hormone that causes the adrenal glands to make cortisol. The extra ACTH is made either by a tumor in the pituitary gland (called Cushing's disease) or by a tumor somewhere else (called ectopic ACTH secretion). Mifepristone blocks the action of cortisol in the body. The drug has been used safely to treat a few people with Cushing's syndrome and patients with certain kinds of cancer, gynecological diseases and psychiatric disorders. People between 18 and 85 years of age with Cushing's syndrome caused by EXCESS ACTH secretion may be eligible for this study. Candidates are admitted to the hospital for evaluation to confirm Cushing's syndrome and to determine its cause. The evaluation includes blood and urine tests, imaging tests, dexamethasone and corticotropin-releasing hormone tests and inferior petrosal sinus sampling. Patients determined to have Cushing's syndrome due to ECTOPIC ACTH secretion undergo imaging studies (CT, MRI and a nuclear medicine scan) and begin mifepristone therapy. Participants remain in the hospital for the following tests and procedures: * Physical examination, electrocardiogram (EKG) and blood and urine tests * Completion of medical questionnaires * DEXA scan to determine bone mineral density and body composition * Glucose tolerance test * Urine pregnancy test and ultrasound to measure uterine lining thickness (for women) Patients take mifepristone by mouth 3 times a day. The dose is increased every week or so until symptoms improve or the highest dosage allowed is reached. Patients may remain in the hospital for all or part of the dose-finding part of the study. During this period (usually 2 to 4 weeks), blood pressure, glucose tolerance and blood chemistries are measured and EKG and urinalysis done every 5 to 14 days. When the mifepristone dose is stable patients remain on that dose for at least 2 weeks and are then re-evaluated. Patients then return to the hospital for evaluations every 3 months. Those who do well on the drug may continue to take it for up to 12 months.

Interventions

  • MifepristoneDrug

Arms1

  • Experimental

    Prospective, open-label, study of mifepristone

    Eligible subjects will start study treatment at the dose of 600 mg/day (given as one 200 mg tablet tid, per os). Total duration of treatment will not exceed 12 months. At the end of 12-month treatment, investigators may petition to extend treatment on a case-by-case basis.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Glycemic Disorders Improved or Normalized

    Time frame · 8 weeks at steady dose

    Registry description

    Criteria for improvement or normalization of glycemic disorders: A. For diabetic patients (known or diagnosed at pre-inclusion visit) * Decrease in HbA1c \> 0.3% B. For patients with IGT * Normalization of OGTT (2-hour glucose plasma level after 75 g OGTT \< 7.8 mmol/L (140 mg/dL) D. For patients with IFG If impaired fasting glucose is also associated with impaired glucose tolerance during OGTT at pre-inclusion: \- Normalization of OGTT (2-hour glucose plasma level after 75 g OGTT \< 7.8 mmol/L (140 mg/dL) If impaired fasting glycemia is associated with normal OGTT at pre-inclusion (except at T0): \- Normalization of fasting plasma glucose (fasting plasma glucose \< 5.5 mmol/L (100 mg/dL)

Secondary outcomes(1)

  1. Features of Cushing's Syndrome

    Time frame · 8 weeks at steady dose

    Registry description

    Criteria for secondary glycemic disorder improvement of clinical symptoms attributable to the Cushing's syndrome A. For diabetic patients * Improvement of the following parameters: glycemic profile, fasting blood glucose, fructosamine, 2-hour OGTT (for diabetics diagnosed at screening) * Number of anti-diabetics treatment or dose of anti-diabetics treatment for diabetic patients already on diabetes treatment at inclusion * Doses of insulin for insulin-treated patients B. For patients with IGT * HbA1c * Fructosamine C. For patients with IFG * HbA1c * Fructosamine D. For all patients * Fasting plasma insulin * Area Under the Curve of OGTT results when OGTT performed * HOMA index

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· 8 weeks at steady dose

Glycemic Disorders Improved or Normalized

GroupValue (participants)
Mifepristone2
Secondary and other outcome results(1)
Secondary outcomeNumber· 8 weeks at steady dose

Features of Cushing's Syndrome

GroupValue (participants)
Prospective, Open-label, Study of Mifepristone2

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
MifepristoneSingle arm. Study medication was to be administered at a total daily dose of 600 mg (given as one 200 mg tablet tid, per os) starting on the day of inclusion. This dose was to be maintained during the whole study except in case of suspicion of adrenal insufficiency, in which case the dose was temporally stopped for 2 to 3 days and restarted at a lower dose of 400 mg daily until the end of the study.–9 / 1717 / 17

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 85 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
* INCLUSION CRITERIA: Subjects will be included if they have ALL of the three following criteria: 1. Hypercortisolism from Cushing's syndrome caused by ACTH ectopic secretion AND 2. Glycemic disorder that is considered to be caused or worsened by the hypercortisolism AND 3. At least one symptom attributable to the Cushing's syndrome. EXCLUSION CRITERIA: * Evidence for Cushing's disease as judged by positive inferior petrosal sinus sampling or a lesion on pituitary MRI with positive CRH test * Suspected or known adrenocortical cancer or adenomas, as judged by ACTH values less than 10 pg/ml and adrenal mass * Subjects with cyclic Cushing's syndrome defined by any measurement of Urinary Free Cortisol over the previous 2 months less than 2 N * Children (age less than 18) and patients over 85 years * Pregnant or lactating women. A urinary pregnancy test will be performed in women of childbearing potential unless they have a history of menopause prior to Cushing's syndrome or hysterectomy * Life expectancy less than two months * Surgery planned within 8 weeks after inclusion, especially bilateral adrenalectomy * Uncontrolled diabetes (plasma glucose greater than 15.0 mmol/L (270 mg/L) and/or HbA1c greater than 10%) * Uncontrolled hypertension (blood pressure greater than 180/110 mmHg) * Recent (less than two weeks prior to inclusion) initiation of corrective treatments for depression * Clinically significantly impaired cardiovascular function (e.g. stage IV cardiac failure) * Severe liver disease (liver enzymes greater than or equal to 3 x the institutional upper limit of normal range) * Severe renal impairment (serum creatinine greater than or equal to 2.2 mg/dl or creatinine clearance less than 30 ml/min) * Severe hypokalemia (plasma K below 3.0 mmol/L) * Uncontrolled severe active infection * In women, known endometrial cancer, history of endometrial hyperplasia or vaginal bleeding of unknown cause * Premenopausal women with hemorrhagic disorders or on anticoagulants * Recent (less than two weeks prior to inclusion) initiation of or significant change in dose of anti-tumor therapy * Previous treatment with approved or experimental steroidogenesis inhibitors, somatostatin analogues within one week of admission (eight weeks for patients on octreotide LAR or on lanreotide autogel) * Plasma mitotane concentration greater than 5 microgram/ml * Impaired mental capacity or markedly abnormal psychiatric evaluation that precludes informed consent * Body weight over 136 kg, which is the limit for the tables used in the scanning areas * Inherited porphyria * Positive pregnancy test at inclusion * Use of antiretroviral agents, midazolam, cabergoline, erythromycin, or grapefruit juice within two weeks of the study

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